Erythropoiesis in anemia of rencl failure and malignancy : Studies on erythropoietin, iron, and transferrin receptor : by Soheir Beshara

Sammanfattning: Erythropoietin (Epo) and iron are essential requirements for erythropoiesis. Serum transferrin receptor (S-TfR) is a marker of total erythropoiesis and tissue iron availability. In patients with renal insufficiency, successful renal transplantation leads to correction of anemia and improvement in erythropoiesis. Recombinant human erythropoietin (rHuEpo) has been shown to correct anemia in patients with solid tumors. Adjustment of the iron status remains a prerequisite for correction of the anemia. The aim of this work was to study erythropoiesis following renal transplantation and in patients with prostatic adenocarcinoma receiving rHuEpo therapy. Pharmacokinetics and red cell utilization of iron(III) hydroxide-sucrose complex were also studied.Follow-up of renal transplant patients showed a gradual increase in S-Epo levels, accompanied by a parallel increase in S-TfR levels, with a median lag period of 3 weeks between the two peaks. Hemoglobin (Hb) correction followed the S-TfR peak after a second lag period. These results indicate that improvement in erythropoiesis after renal transplantation seems to occur by means of expansion of the erythroid marrow subsequent to an Epo peak. This expansion precedes Hb normalization. Iron deficiency may occur after transplantation- as a result of an increase in iron utilization.Patients with prostatic adenocarcinoma and anemia displayed low S-TfR, hypoferremia in spite of abundant iron stores, and elevated plasma viscosity. Following treatment with rHuEpo, four patients showed a median Hb increase of 20 g/l, while in three patients there was a median increase of 17 g/I, but each of the latter three required blood transfusion on one occasion. The results indicate that suppression of erythropoiesis can be mainly explained by the depressed marrow activity. The altered hemorheology might contribute to this anemia, which could possibly be corrected with rHuEpo.Positron emission tomography (PET) was applied to study the distribution characteristics of a single intravenous injection of 100 mg iron(III) hydroxide-sucrose complex (Venofer®) labeled with 52Fe and followed for some hours. There was pronounced radioactive uptake by the liver, spleen and bone. The radioactive uptake by the macrophage-rich spleen demonstrates the reticuloendothelial uptake of this iron preparation, with its subsequent effective release for marrow utilization. Red cell utilization of the iron complex, followed for four weeks, ranged from 59% to 97%. A kinetic analysis using a three-compartment model (namely blood pool, reversible, and irreversible tissue pools) showed a fairly high distribution volume but a low influx rate constant in the liver as compared with the bone marrow. The bone marrow influx rate constant was steady, indicating non-saturation of the transport system.